title: Role of vascular channels as a novel mechanism for subchondral bone damage at cruciate ligament entheses in osteoarthritis and inflammatory arthritis.
abstract: OBJECTIVE
  The purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA).
  
  
  METHODS
  Normal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion.
  
  
  RESULTS
  Vascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%).
  
  
  CONCLUSIONS
  The findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK Leeds Musculoskeletal Biomedical Research Unit, National Institute for Health Research, Chapel Allerton Hospital, University of Leeds, Leeds, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Binks
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Gravallese
authors.affiliation: Department of Radiology, Galway University Hospitals, Galway, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Bergin
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK Leeds Musculoskeletal Biomedical Research Unit, National Institute for Health Research, Chapel Allerton Hospital, University of Leeds, Leeds, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodgson
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK Leeds Musculoskeletal Biomedical Research Unit, National Institute for Health Research, Chapel Allerton Hospital, University of Leeds, Leeds, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Tan
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Matzelle
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK Leeds Musculoskeletal Biomedical Research Unit, National Institute for Health Research, Chapel Allerton Hospital, University of Leeds, Leeds, UK.
authors.forename: D
authors.initials: D
authors.lastname: McGonagle
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK Leeds Musculoskeletal Biomedical Research Unit, National Institute for Health Research, Chapel Allerton Hospital, University of Leeds, Leeds, UK.
authors.forename: A
authors.initials: A
authors.lastname: Radjenovic
mesh_terms: D000368:Aged; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000473:pathology*; D001169:Arthritis, Experimental / Q000473:pathology*; D001808:Blood Vessels / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology*; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000473:pathology*; D016119:Posterior Cruciate Ligament / Q000473:pathology*
keywords: Inflammation; Knee Osteoarthritis; Magnetic Resonance Imaging; Osteoarthritis; Rheumatoid Arthritis